Skip to main content

Congenital Erythropoietic Porphyria

What is Congenital Erythropoietic Porphyria (CEP)?

Congenital erythropoietic porphyria (CEP) is a very rare inherited metabolic disorder resulting from the deficient function of a specific enzyme, uroporphyrinogen III synthase (URO-synthase), in the heme biosynthetic pathway. Due to the impaired function of this enzyme, excessive amounts of particular porphyrins accumulate, particularly in the bone marrow, plasma, red blood cells, urine, teeth, and bones. The two major symptoms of this disorder are: 1) marked sensitivity of the skin to sunlight and some types of artificial light, such as fluorescent lights, in all patients, and 2) anemia which in severely affected patients requires chronic red blood cell transfusions. These patients are transfusion-dependent and may benefit from bone marrow transplantation. In less severely affected patients, the red blood cells have a shortened life-span, and mild anemia may result.

After exposure to sunlight, the photo-activated porphyrins in the skin cause blistering and the fluid-filled sacs can rupture, and the ruptured lesions often get infected. These infected lesions can lead to scarring, bone loss, and deformities. The hands, arms, and face are the most commonly affected areas. Increased hair growth (hypertrichosis) on sun-exposed skin, brownish-colored teeth (erythrodontia), and reddish-colored urine are common. There may be bone fragility due to expansion of the bone marrow and vitamin deficiencies, especially vitamin D. The spleen can be enlarged, particularly in anemic patients with CEP.

How is Congenital Erythropoietic Porphyria inherited?

CEP is inherited as an autosomal recessive genetic disorder. Recessive disorders occur when an individual inherits two copies of an abnormal gene for the same trait or disease, one from each parent. Typically, there is no family history of the disease, and neither parent has symptoms, but each carries a defective gene that they can pass to their children. The risk for two carrier parents to both pass the defective gene and have an affected child is 25% with each pregnancy. If an individual receives one normal gene and one disease-causing gene, the person will be a carrier for the disease, and will not have any symptoms.

How is Congenital Erythropoietic Porphyria diagnosed?

The diagnosis of CEP may be suspected when reddish-colored urine is noted at birth in the diaper or later in life. This finding, or the occurrence of skin blisters on sun or light exposure, should lead to a clinical evaluation and specialized laboratory tests. The diagnosis can be made by testing the urine for markedly elevated levels of the porphyrins, uroporphyrin I and coproporphyrin I. Diagnostic confirmation requires the demonstration of the URO-synthase enzyme deficiency and/or the specific alterations in the URO-synthase gene. For genetic testing, DNA is extraction from a blood sample and is used to look at the URO-synthase gene to see if there are DNA changes that that can cause the disease, called mutations. Genetic testing is recommended for all patients, as the specific mutation(s) provides information about the severity of the disease.

Once the UROS mutations have been identified, family members can be tested to determine who carries the disease-causing gene. Prenatal and preimplantation genetic diagnoses are available for subsequent pregnancies in CEP families, if the underlying genetic mutations are known. Other reproductive options are available to avoid the birth of an affected child.

What are treatments for Congenital Erythropoietic Porphyria?

Avoiding exposure to sunlight is the most important way to manage symptoms for patients with CEP. Patients need to wear protective clothing, and have windows tinted in their cars and homes. Blood transfusions to correct anemia are required in severe cases, to reduce porphyrin production by the marrow. In severely affected, transfusion-dependent patients, a successful bone marrow transplant will replace the CEP marrow and correct the metabolic defect. Patients who have successful bone marrow transplants no longer have sun-sensitivity.